SETD2
SETD2 (Histone-lysine N-methyltransferase SETD2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Renal cell carcinoma, Leukaemia, Non-Hodgkin lymphoma and 5 more.
Overview
Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation.
CIViC holds 3 clinical evidence items and 0 assertions across 2 variants, naming Akt Inhibitor MK2206, PI3Kbeta Inhibitor AZD8186, Samotolisib and Anti-PD1 Monoclonal Antibody and others. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes genetic literature 0.38, affected pathway 0.76, literature 0.99, genetic association 0.36, somatic mutation 0.94). IntOGen calls it a driver in 34 cohorts (1 activating, 33 loss-of-function), covering Acute Lymphoblastic Leukaemia, Renal Clear Cell Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Oesophagogastric Adenocarcinoma, Ewing Sarcoma, Glioblastoma and others. In OnCo, 1 product record names it (Temsirolimus).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · SETD2 (Histone-lysine N-methyltransferase SETD2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Renal cell carcinoma, Leukaemia, Non-Hodgkin lymphoma and 5 more.
- 1 · What it is
SETD2 (Histone-lysine N-methyltransferase SETD2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Renal cell carcinoma, Leukaemia, Non-Hodgkin lymphoma and 5 more.
- 2 · What goes wrong in cancer
Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro.
- 3 · How drugs use it
No product in this corpus aims at SETD2 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:18420 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9BYW2 (protein name, function text, keywords and locations (REST API)); CIViC gene SETD2 (3 evidence items, 0 assertions, 2 variants; diseases: Clear Cell Renal Cell Carcinoma, Malignant Mesothelioma (GraphQL API, CC0)); Open Targets ENSG00000181555 (association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.59, renal cell carcinoma 0.70, melanoma 0.64, neuroendocrine neoplasm 0.52, acute lymphoblastic leukaemia 0.64, B-cell chronic lymphocytic leukaemia 0.51 (GraphQL API, CC0)); IntOGen SETD2 (driver in 34 cohorts (Act 1, LoF 33); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR). Location: Nucleus; Chromosome (UniProt). Locus 3p21.31 (HGNC).
- Renal cell carcinoma: Open Targets association 0.70 with renal cell carcinoma (MONDO_0005086); IntOGen driver in 5 cohorts (CCRCC, PRCC, RCC)
- Leukaemia: Open Targets association 0.66 with leukaemia (MONDO_0005059)
- Non-Hodgkin lymphoma: Open Targets association 0.64 with non-Hodgkin lymphoma (MONDO_0018908)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 3 cohorts (PAAD, PANCREAS)
- Mesothelioma: IntOGen driver in 3 cohorts (PLMESO)
- Skin cancer: Open Targets association 0.61 with skin cancer (MONDO_0002898)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 6 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 33 cohorts; CIViC holds 3 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Malignant Mesothelioma; Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"SETD2" OR ABSTRACT:"SETD2" OR TITLE:"SET domain containing 2, histone lysine methyltransferase" OR ABSTRACT:"SET domain containing 2, histone lysine methyltransferase" OR TITLE:"Histone-lysine N-methyltransferase SETD2" OR ABSTRACT:"Histone-lysine N-methyltransferase SETD2" OR TITLE:"HIF-1" OR ABSTRACT:"HIF-1" OR TITLE:"KIAA1732" OR ABSTRACT:"KIAA1732" OR TITLE:"FLJ23184" OR ABSTRACT:"FLJ23184") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about SETD2, not a curated reading list.
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